psma response in metastasized hormone sensitive prostate cancer - enzalutamide

Conditions: Prostate Cancer

Summary: psma-pet/ct response measurements after lhrh agonist and upfront enzalutamide therapy in men diagnosed with de novo metastasized hormonal sensitive prostate cancer.

rationale: men, newly diagnosed with metastasized prostate cancer on psma pet/ct, who start on standard hormonal therapy, are additionally treated with either upfront chemotherapy or upfront extra androgen-receptor targeted agents ('arta'), as per guidelines' recommendations. the benefit in overall survival of these two options is similar, but important differences exist in patient-specific efficacy, costs, side-effects, and impact on quality of life. no predictive factors are available to individualize treatment choice. currently, a one-size-fits-all strategy with hormonal therapy plus chemotherapy is usually followed. objective: to assess the predictive value of early response measurements on psma-pet/ct for therapy success, defined as time to development of castration-resistant prostate cancer (crpc), in order to personalize treatment choice. study design: prospective, single arm, open label, non-interventional, non-therapeutic observational cohort study. study population: patients \>18 years with newly diagnosed, histologically proven prostate cancer with \>3 skeletal or visceral metastatic lesions on the psma-pet/ct, who are considered eligible for upfront therapy (enzalutamide) in addition to standard hormonal therapy. main study parameters/endpoints: primary parameter: predictive value of early response on psma-pet/ct to upfront therapy, according to percist criteria. primary endpoint: time to development of crpc. secondary parameters: predictive value of early response on psma-pet/ct to hormonal therapy; predictive value of baseline psma-pet/ct, analysis of response in different subgroups of patients: e.g. high versus low tumour load, high versus low psa, high versus low gleason score. secondary endpoint: time to initiation of second line therapy after castration-resistant disease has been found. nature and extent of the burden and risks associated with participation, benefit, and group relatedness: patients will be treated according to standard of care, including baseline psma-pet/ct. the timing of follow-up psma-pet/ct imaging will be standardized. instead of imaging at biochemical or clinical signs of disease progression, one psma-pet/ct will be performed after two months of hormonal therapy, one psma-pet/ct will be performed after two months of upfront therapy. each psma-pet/ct scan will require an extra visit (2-3 hours) and a limited radiation burden after intravenous injection of psma. the additional information from the standardized follow-up psma-pet/ct scans will not be used for clinical decision-making.

Eligibility criteria:
inclusion criteria: * men \>18 years of age. * mentally competent and understanding of benefits and potential burden of the study. * written and signed informed consent. * histological confirmed diagnosis of adenocarcinoma of the prostate. * indicated to start on hormonal therapy (any lhrh agonist or antagonist). * indicated to start on upfront therapy (enzalutamide). * any initial psa. * any gleason score. * any t-stage. * any n-stage. * stage m1, with multiple / high volume metastasis: more than three (\>3) metastatic lesions (any combination of either lymph node metastasis outside of pelvis, bone metastasis, or visceral metastasis), as seen on psma-pet/ct-imaging. as these patients are treated with palliative intent. exclusion criteria: * concomitant malignancy (except from bcc of the skin). * history of prior diagnosed or treated pca. * any unrelated illness (e.g. active infection, inflammation or laboratory abnormalities) that in the judgment of the investigator will significantly affect patient's clinical status and/or outcome of the study. * any known allergy for the upfront therapy. * any known allergy for lhrh agonist or antagonist.